tbuckley/cabot-search huggingface dataset:
Abstract 11157: A Rare Case of Concomitant Dual Genetic Cardiomyopathies in a Patient Complicated by Stroke
Authors: Mark P Ranasinghe, Cecilia Kwok, Han Lim, Simon Bodek, Mark Nolan
Journal: Circulation (2022)

Background: Very little evidence exists on the prevalence of co-existing cardiomyopathies. We report in this case a highly atypical presentation of concurrent arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) likely attributable to simultaneous separate somatic mutations, complicated by stroke. Case: A 60-year-old male with a history of rheumatoid arthritis, sleep apnoea and obesity with no significant coronary disease referred for review of asymptomatic ECG abnormalities was found to have severe asymmetrical left ventricular (LV) wall thickening with apical segment akinesis and an LV apex mass on echocardiogram. She had a family history of early sudden cardiac death, with an otherwise unremarkable history and physical examination. Clinical Course: Cardiac MRI (CMR) subsequently demonstrated aneurysmal dilatation of LV apical segments with a 17x13mm thrombus present. Systolic anterior mitral leaflet motion was seen, and a dilated right ventricle (RV) with 240ml end-diastolic volume and 27% ejection fraction. "Accordion" sign was present in the sub-tricuspid RV free wall with dyskinesia, and ECGs confirmed presence of epsilon waves. One week after CMR, she suffered a large left middle cerebral artery (MCA) stroke in the setting of warfarin cessation due to echocardiography-suggestive absence of thrombus. Discussion: Genetic analysis revealed a mutated Plakophillin 2 (PKP2) gene, and FHOD3 gene associated with HCM of uncertain significance. The diagnosis was concomitant genetic cardiomyopathies of ARVC and HCM complicated by large LV apical aneurysm and thrombus culminating in left MCA stroke. PKP2 mutations to date have not been associated with hypertrophic phenotypes. This case therefore demonstrates the unlikely 1 in 2,500 incidence of coexistence of two separate cardiomyopathies likely attributable to simultaneous separate somatic mutations, while also highlighting the central role of CMR in investigation and diagnosis of RV pathology. In addition to this case, prior studies have also shown echocardiography can only identify 50% of ARVC cases identified by CMR, suggesting that selective use of CMR may double the number of identified cases of this life-threatening disease.
Abstract 12520: Pathophysiologic Basis of Angina Symptoms in Women With Nonobstructive Atherosclerosis Using Artificial Intelligence-Enabled Coronary Plaque Analysis
Authors: Balaji Tamarappoo, Guadalupe Flores Tomasino, Vinicius Calsavara, Rebekah Park, Andrew Lin, Eileen M Handberg, Chrisandra Shufelt, Leslee J Shaw, Daniel Berman, Piotr J Slomka, Matthew Budoff, Carl J Pepine, C. Noel Bairey Merz, Damini Dey
Journal: Circulation (2022)

Background: Coronary CT angiography (CCTA) artery plaque characteristics including low attenuation and positive remodeling are associated with future myocardial infarction. Associations between angina symptoms and plaque characteristics are unknown. Objective: To examine relationships between quantitative plaque characteristics and angina in women with nonobstructive plaque using artificial intelligence (AI)-enabled plaque analysis. Methods: A sample of women with angina and CCTA nonobstructive plaque (&lt;50% luminal stenosis) enrolled in the WARRIOR trial (NCT 03417388) was studied with validated AI software (Autoplaque 3.0, Cedars Sinai). Complete coronary plaque composition was expressed as noncalcified (NCP), low attenuation noncalcified plaque (LAP, as NCP&lt;30 Hounsfield Units) and calcified plaque (CP) (Figure). Plaque burden was defined as plaque volume x 100%/vessel volume. Angina was quantified by the Seattle Angina Questionnaire angina frequency domain. Relationships between plaque characteristics and angina frequency at enrollment were evaluated using linear and logistic regression in women with total plaque volume &gt;200mm 3 . Results: Among 72 women (age 61.8±10.1 yrs, BMI 30.3±7.2 kg/m2, LDL-C 86.5±27.9, HDL 55.8±17.3, total cholesterol 164.2±37.7 mg/dl, respectively), total plaque volume was 460.1±192.8mm 3 and NCP burden was 50.3± 7.1%. By linear regression, worsening angina frequency was related to increasing NCP burden (β=-0.76, p=0.011). In a logistic regression model, every unit increase in NCP burden was related to ~11% excess risk (1.108, 1.023-1.2, p=0.012) of monthly angina (angina frequency score ≤99). Conclusion: In women with nonobstructive coronary plaque and angina in the WARRIOR trial, higher CCTA NCP burden is associated with more frequent angina. Further work with quantitative AI analysis of CCTA from the WARRIOR trial will validate these preliminary findings.
Abstract 12661: Prognostic Significance of Tubular Injury Biomarkers in Heart Failure With Preserved Ejection Fraction (HFpEF)
Authors: Oday Salman, Chenao Qian, Jordana Cohen, Qasim Jehangir, Payman Zamani, Christina Ebert, Danielle Greenawalt, Zhaoqing Wang, Lei Zhao, Ching-Pin Chang, David A Gordon, Francisco Ramirez-Valle, Thomas P Cappola, Julio A Chirinos
Journal: Circulation (2022)

Background: The onset and progression of CKD in HFpEF may be driven by different etiologies, including tubular injury, glomerular disease or interstitial remodeling. We assessed the prognostic significance of tubular injury assessed with a combination of plasma protein biomarkers. Methods: We analyzed data and samples from the TOPCAT trial. We utilized the SomaScan assay to measure tubular injury biomarkers: Alpha-1 microglobulin (A1M), Beta 2 microglobulin (B2M), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule 1 (KIM1), and interleukin 18 (IL-18). Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between factor scores and: (1) All-cause mortality; (2) The composite of death or heart failure hospital admission (DHFA). All hazard ratios (HR) are standardized (per unit increase in z score) to facilitate comparisons. Linear regression was used to assess the relationship of each factor to 4,746 other proteins, followed by pathway analyses. Results: There were 2 underlying factors: factor 1 was associated predominantly with KIM1, whereas factor 2 was strongly associated with NGAL. Both factors were associated with estimated GFR. Factor 1 was predominantly associated with diabetes, whereas factor 2 was predominantly associated with a lower mean arterial pressure. In a model that included the 2 factors, both were significantly and independently associated with DHFA (Factor 1 HR=1.75; 95%CI=[1.47,2.07]; P&lt;0.0001; Factor 2 HR=1.37; 95%CI=[1.17,1.62]; P=0.0001), but only factor 1 was significantly associated with death (Factor 1 HR=1.22; 95%CI=[1.06,1.40]; P=0.0046; Factor 2 HR=1.23; 95%CI=[0.98,1.54]; P=0.066). In analyses that adjusted for estimated GFR and the MAGGIC risk score, Factor 1 was significantly associated with death and DHFA, whereas Factor 2 was only associated with DHFA. These factors were associated with pathways related to immunity, fibrosis, oxidative stress, cell death, and myocardial remodeling. Conclusion: Tubular injury is associated with adverse outcomes in HFpEF. This relationship is independent of baseline GFR, suggesting that ongoing injury contributes to poor outcomes and may represent a target for therapy.
Abstract 12620: Effects of Financial Status on Engagement in Self-care in Rural Caregivers With Cardiovascular Risk Factors
Authors: Misook L Chung, Jennifer Miller, Terry A Lennie, Frances J Feltner, Debra K Moser
Journal: Circulation (2022)

Introduction: Caring for adults with chronic illnesses increases the risk of developing cardiovascular disease (CVD). Engaging in self-care of healthy behaviors is critical for caregivers, but it may be more difficult due to financial hardship and psychological distress among those living in socioeconomically distressed rural areas. The study's purpose was to examine the association of financial status with engagement in self-care and whether this association is mediated by depressive symptoms in rural caregivers. Methods: We used baseline data from 300 rural caregivers (mean age 55 years, 76% female) with at least 2 CVD risk factors participating in a CVD risk reduction intervention trial. They provided data on financial status (3 groups: more than enough, enough, and not enough to make ends meet), depressive symptoms (Patient Health Questionnaire), self-care engagement (MOS-Specific Adherence Scale), caregiving time/difficulty (Oberst Caregiving Burden Scale), and physical assessments for estimating Framingham CVD risk score. Mediation analysis with a multi-categorical antecedent was conducted controlling Framingham risk score and caregiving time/difficulty. Results: Those with more than enough (27%), enough (56%), and not enough (56%) to make ends meet had similar Framingham risk scores (M = 12.3, P = .61). Compared to the more than enough group (Figure 1), the not enough group had lower self-care engagement scores (direct effect = -6.48) that were reduced further by the influence of depressive symptoms (indirect effect = -1.19). The results were similar for the enough to make ends meet group (direct effect= - 2.67; indirect effect = -.70). Conclusion: Poor financial status was directly associated with decreased engagement in self-care and indirectly associated through increased depressive symptoms. Promoting self-care strategies should include managing depressive symptoms for rural caregivers with a high risk of CVD who report financial hardship.
Abstract 12692: Central Sensitization in Women With Ischemia and No Obstructive Coronary Artery Disease: A Pilot Study
Authors: Esha K Dave, Sneha Thandra, Daniel E Harper, vinita singh, Avni Ahuja, Ana Leon, Arielle Schwartz, Fauzia Rashid, Laura P Kimble, Puja K Mehta
Journal: Circulation (2022)

Introduction: Myocardial ischemia with no obstructive coronary arteries (INOCA) is more common in women and associated with adverse cardiovascular outcomes. INOCA patients have recurrent chest pain and reduced quality of life, and therapeutic strategies are poorly defined. Central nervous system factors can promote and maintain spontaneous clinical pain. We explored central sensitization in INOCA. Methods: Twenty-nine women diagnosed with INOCA based on coronary angiography were enrolled. Baseline demographics, risk factors, and angina burden by the Seattle Angina Questionnaire (SAQ) was assessed. Generalized pain hypersensitivity was assessed using the validated Central Sensitization Inventory (CSI), with scores ≥40 indicating the presence of central sensitization. Functional capacity was determined by Duke Activity Status Index (DASI). A DASI score ≤34 is prognostic of major adverse cardiac events. Depressive symptoms were assessed using the Beck Depression Inventory. Descriptive statistics and Pearson correlations were performed; p-value ≤.05 was considered significant. Results: Mean age was 55.4±10 years and body mass index (BMI) was 30.1±7 kg/m 2 . Cardiac risk factors were prevalent with 59% hypertension, 55% hyperlipidemia, and 21% diabetes. SAQ scores indicated a high angina burden: 49.3±25.7 (angina frequency) and 39.3±27.6 (angina stability). Mean CSI score was 40.5±17, and 62% had CSI scores ≥40, indicating central sensitization. Mean DASI score was 33.3±18.6. A majority (52%) had a DASI score ≤34, indicative of guarded prognosis. CSI scores correlated positively with depression (r=0.78, p=0.00001) and BMI (r=0.39, p=0.04), and negatively with DASI (r=-0.36, p=0.05), indicating impaired physical functioning in those with higher levels of central pain sensitivity. Conclusions: Nearly two-thirds of women with INOCA have central sensitization. Central pain amplification is associated with angina, depression, obesity, and a limited functional capacity in mid-life INOCA women. The role of the central nervous system in persistent chest pain should be further investigated and may lead to novel therapeutic strategies.
Abstract 12357: Prevalence and Impact of Obesity Status in Current Randomized Controlled Trials of Catheter Ablation for Treatment of Atrial Fibrillation: A Systematic Review
Authors: ahmad Aroudaky, Muaaz Almerstani, Eh Khaing, Gleb Haynatzki, John Schleifer, Jason Payne, Arthur Easley, Faris Khan, John R Windle, Shane Tsai, Daniel R Anderson, Niyada Naksuk
Journal: Circulation (2022)

Introduction: The prevalence of obesity among patients with AF and its impact on catheter ablation outcomes remain controversial. We aimed to examine the proportion of obese participants enrolled in current AF ablation RCTs and outcomes of ablation among patients with obesity. Methods: We systematically searched PUBMED for RCTs examining catheter ablation for treatment of AF published between 01/2019 to 03/2022. When mean and standard deviation (SD) were available, normal distribution was assumed and a z-score was used to estimate the proportion of obese participants. A trial was classified as group A and B when conducted in countries where obesity is defined as BMI ≥30 and ≥25 kg/m 2 , respectively. Results: Of 26 RCTs comprising 1,582 participants, 19 (73.1%) trials reported the BMI of study participants, but only 2 (7.7%) specified the proportion of obesity (15.5% and 39.0%). Two trials excluded participants with BMI&gt;35 kg/m 2 . In group A (N 1 =17), the mean BMI was 28.8±1.4 kg/m 2 with estimated obese participants of 39.7% (IQR 38-45 kg/m 2 ). The mean BMI in group B (N 2 =9) was 24.9±1.1 kg/m 2 with estimated obese participants of 47.1% (IQR 37-50 kg/m 2 ), Figure. Subgroup analysis examining the effect of catheter ablation according to the BMI status was not reported in any RCTs. Bivariate or multivariate analysis evaluating the effect of BMI or body weight were used in only 4 (15.4%) RCTs. The results suggested that BMI or body weight did not affect their main findings with risk ratio of 0.97-1.00. Conclusion: Current AF ablation RCTs underreport the actual proportion of participants with obesity. However, using the available mean BMI of the study subjects, concomitant obesity among AF patients was highly prevalent and identified in 40-50%. The impact of obesity on the main findings is not fully reported; thus, efficacy of AF ablation among obese patients could not be concluded.
Abstract 11647: Association of Breast Arterial Calcification With Clinical Outcomes and Mortality
Authors: Quan M Bui, Alexandra V Sykes, Tara Allen, Nora Belrose, Nitesh Nerlekar, Richard Mantey, Junhao Wang, Mohammad Eghtedari, Lori Daniels
Journal: Circulation (2022)

Introduction: Breast arterial calcification (BAC), seen on mammography, has emerged as a risk stratification tool and surrogate marker of cardiovascular disease (CVD). Studies evaluating the association of BAC with clinical outcomes are limited. Methods: This single-center, retrospective study included 14,544 women who had a digital mammogram from 2008-2016. BAC was quantified with the Bradley score using an automated algorithm based on a trained, deep neural network (CureMetrix). The presence of BAC was defined as Bradley score &gt;10. Clinical outcomes were collected via medical records using ICD-10 diagnoses. Cox regression models were used to evaluate the association between BAC (continuous and binary) and clinical outcomes including mortality and composite outcome (mortality, stroke, and myocardial infarction). Models were adjusted for age, diabetes, medications, race, current smoking, systolic blood pressure, total &amp; HDL cholesterol, and prior CVD diagnosis. Results: The mean age was 54.7 ±11.0 years with 8% diabetes, 30% hypertension, 30% hyperlipidemia and 5% smokers. BAC was present in 13%. Over a mean follow-up of 4.2 years, there were 1,687 deaths (6.8%) and 2,113 composite outcomes (8.5%). On multivariable analysis, each 10-point increase in BAC score was significantly associated with clinical outcomes: mortality (aHR 1.05 [95% CI 1.02-1.08], p &lt; 0.001) and composite outcome (aHR 1.07 [95% CI 1.04-1.09], p &lt; 0.001). With BAC as a binary variable, women with BAC had a 1.52 (95% CI 1.22-1.89) higher risk of mortality and a 1.72 (95% CI 1.40-2.11) higher risk of composite outcome compared to those without BAC. Conclusion: BAC is significantly associated with clinical outcomes, including mortality and CVD. Further study is needed to confirm these findings.
Abstract 12182: Cardiac Transcriptome Remodeling and Impaired Bioenergetics in Single Ventricle Congenital Heart Disease
Authors: Anastacia M Garcia, Lee S Toni, Genevieve C Sparagna, Raleigh Jonscher, Anis Karimpour-Fard, Angela N Baybayon-Grandgeorge, Ashley E Pietra, Brian L Stauffer, Carmen C Sucharov, Shelley D Miyamoto
Journal: Circulation (2022)

Introduction: Single Ventricle congenital heart disease (SV) encompasses a group of cardiac abnormalities where improper development of the heart results in only one functional pumping chamber. From a molecular standpoint, how the myocardium adapts to the chronic altered hemodynamic conditions of SV physiology, and the mechanisms implicated in the transition to heart failure (HF) which is common in the SV population, are poorly understood. Here, we test the hypothesis that metabolic remodeling represents a pathophysiologic mechanism of heart failure progression in SV. Methods: We performed comprehensive multi-omics analysis (transcriptomics, metabolomics, and lipidomics) of the SV myocardium from both failing (SVHF, N=15) and non-failing (SVNF, N=9) SV subjects, compared with biventricular non-failing controls (BVNF, N=4). Furthermore, we assessed functional components of mitochondrial bioenergetics in each of these populations. Results: Integrated multi-omics analysis demonstrated dysregulation of multiple metabolic pathways in the failing SV heart (A). Functional cardiac bioenergetics analysis revealed decreased mitochondrial carnitine palmitoyl transferase activity (B) and mitochondrial dysfunction (C), with corresponding decreases in tricarboxylic acid cycle metabolites, high energy phosphates, and lipid intermediates in the failing SV heart. Moreover, some of these bioenergetic perturbations precede the onset of overt failure, and are seen in the non-failing SV heart (B-C). Conclusions: Our findings indicate that SV physiology induces myocardial metabolic alterations that limit mitochondrial fatty acid β-oxidation and decrease cardiac energy generation. Together, these data suggest SV patients may be uniquely vulnerable to changes in energetic demand and may benefit from therapeutic strategies aimed at preserving cardiac bioenergetics and preventing cardiometabolic remodeling for the treatment or prevention of HF.
Abstract 12089: Right Coronary Artery Aneurysm in Takayasu Arteritis
Authors: Mahmoud Kabbani, Catherine Teng
Journal: Circulation (2022)

Background: Takayasu arteritis (TA) is a large vessel vasculitis that affects the aorta and its primary branches. The coronary arteries are uncommonly involved. Case Presentation: A 52-year-old man, with a history of TA not on immune suppressants due to recurrent active miliary tuberculosis, was scheduled for open abdominal repair of a multilobulated saccular thoracoabdominal aneurysm. Cardiology was consulted for pre-operative evaluation. His physical exam and EKG were unremarkable. Imaging of his coronaries with CT angiography showed proximal and distal right coronary artery dilation (14 mm) and a intraluminal thrombus. Revascularization surgically or percutaneously was not advised. Additional vascular interventions were postponed until the patient received adequate treatment for his tuberculosis and uncontrolled TA. The patient was started on ASA and warfarin for the intraluminal thrombus and coronary aneurysm. Discussion: Coronary artery aneurysms are rare in TA. When coronaries are involved, ostial stenosis or occlusion is the most common lesion. Invasive coronary angiography is difficult due to diffuse vascular disease and involvement of the aorta. The imaging modality of choice remains a debate. CT angiograms remain a reasonable option for the assessment of coronary involvement. There is no established guideline for the treatment of coronary thrombus in patients with TA. Because coronary aneurysms promote thrombus formation by stasis and abnormal flow conditions, it is reasonable to treat with ASA combined with warfarin as they do in Kawasaki disease. Conclusion: Although rare in TA, coronary aneurysm formation is possible. A coronary angiogram is technically difficult in this group of patients, and CT angiograms remains a safe option to define coronary anatomy. The treatment guidelines are lacking, and ASA combined with warfarin is a reasonable option to reduce myocardial infarction and death.
Abstract 11765: Gender Disparities in Complications Post Atrial Fibrillation Ablation
Authors: Aleesha Kainat, Hassan Alhassan, Harriet Akunor, Joseph Donohue, Samir Saba
Journal: Circulation (2022)

Introduction: Catheter ablation therapy (CAT) is recommended for the management of symptomatic atrial fibrillation (AF). Previous real-world studies using the National Inpatient Sample (NIS) have described a disproportionately higher burden of post-CAT complications in women Hypothesis: We sought to determine whether the prior gender disparities in complications post-CAT for AF still exist. We hypothesize that with increasing CAT proficiency women would be no more likely to suffer complications compared to men Methods: We identified all percutaneous AF CAT hospitalizations in the NIS 2016-2019. We used Inverse-Probability Weighting (IPW) to create a pseudo-population where gender was independent of the following confounders: age, race/ethnicity, primary payor, median income, CHA2DS2VASc and Elixhauser scores, comorbidities including obesity, alcohol use disorder, obstructive sleep apnea, chronic pulmonary disease, and hospital characteristics-region, teaching-status, and bed-size. We compared in-hospital mortality rate, total procedural complications including pericardial (tamponade/effusion/pericarditis); cardiac (heart failure/perioperative MI/shock); respiratory (pneumothorax/respiratory failure); esophageal (perforation/injury); vascular (access-site fistulas/bleeding); and renal (acute kidney injury) between men and women Results: Of the 5,835 AF CATs identified (representing 29,175 nationally), 43.2% were performed in women. Before IPW, women were older, and had higher proportions of comorbidities. After applying weights, baseline characters were well-balanced. In the weighted-cohort, there was no difference in mortality (0.48% vs 0.29%, p=0.52) or total complications (8.3% vs 9.6%, p=0.20). Likewise, pericardial (4.5% vs 4.1%, p=0.26); cardiac (0.3% vs 0.4%, p=0.40); vascular (3.6% vs 3.4%, p=0.37); respiratory (0.7% vs 0.8%, p=0.70); esophageal (0.5% vs 0.4%, p=0.31); and renal (1.2% vs 2.3%, p=0.38) complications, were similar across gender Conclusion: In this real-world cohort, the burden of complications after CAT for AF was similar across gender. Sustained national efforts at maintaining awareness of gender disparities in complications post-AF CAT are needed to keep this new status quo